Metformin 850 mg film-coated tablets

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Metformin is and what it is used for
2. What you need to know before you take Metformin
3. How to take Metformin
4. Possible side effects
5. How to store Metformin
6. Contents of the pack and other information

• are allergic to metformin or any of the other ingredients of this medicine (listed in section 6).
• have liver problems.
• have severely reduced kidney function.
• have uncontrolled diabetes, with, for example, severe hyperglycaemia (high blood glucose), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see "Risk of lactic acidosis" below) or ketoacidosis. Ketoacidosis is a condition in which substances called 'ketone bodies' accumulate in the blood and which can lead to diabetic pre-coma. Symptoms include stomach pain, fast and deep breathing, sleepiness or your breath developing an unusual fruity smell.
• lost too much water from your body (dehydration), due to long-lasting or severe diarrhoea, or if you have vomited several times in a row. Dehydration may lead to kidney problems, which can put you at risk for lactic acidosis (see 'Warnings and precautions').
• have a severe infection, such as an infection affecting your lungs or bronchial system or your kidneys. Severe infections may lead to kidney problems, which can put you at risk for lactic acidosis (see 'Warnings and precautions').
• are treated for acute heart failure or have recently had a heart attack, have severe problems with your circulation (such as shock) or have breathing difficulties. This may lead to a lack in oxygen supply to tissue which can put you at risk for lactic acidosis (see 'Warnings and precautions').
• drink a lot of alcohol.

If any of the above applies to you, talk to your doctor, before you start taking this medicine.

Make sure you ask your doctor for advice, if you:

• need to have an examination such as X-ray or scan involving the injection of contrast medicines that contain iodine into your bloodstream.
• need to have major surgery.

You must stop taking Metformin for a certain period of time before and after the examination or the surgery. Your doctor will decide whether you need any other treatment for this time. It is important that you follow your doctor's instructions precisely.

Talk to your doctor or pharmacist before taking Metformin.

Risk of lactic acidosis

Metformin may cause a very rare, but very serious side effect called lactic acidosis, particularly if your kidneys are not working properly. The risk of developing lactic acidosis is also increased with uncontrolled diabetes, serious infections, prolonged

fasting or alcohol intake, dehydration (see further information below), liver problems and any medical conditions in which a part of the body has a reduced supply of oxygen (such as acute severe heart diseases).

If any of the above apply to you, talk to your doctor for further instructions.

It is important for you to comply with your medication intake, dietary instructions and regular exercise program because this can reduce the risk of lactic acidosis.

Stop taking Metformin for a short time if you have a condition that may be associated with dehydration (significant loss of body fluids) such as severe vomiting, diarrhoea, fever, exposure to heat or if you drink less fluid than normal. Talk to your doctor for further instructions.

Stop taking Metformin and contact a doctor or the nearest hospital immediately if you experience some of the symptoms of lactic acidosis, as this condition may lead to coma.

Symptoms of lactic acidosis include:

• vomiting,
• stomach ache (abdominal pain),
• muscle cramps,
• a general feeling of not being well with severe tiredness,
• difficulty in breathing,
• reduced body temperature and heartbeat.

Lactic acidosis is a medical emergency and must be treated in a hospital.

If you need to have major surgery you must stop taking Metformin during and for some time after the procedure. Your doctor will decide when you must stop and when to restart your treatment with Metformin.

During treatment with Metformin, your doctor will check your kidney function at least once a year or more frequently if you are elderly and/or if you have worsening kidney function.

talk to your doctor promptly for further instructions if

• You are known to suffer from a genetically inherited disease affecting mitochondria (the energy-producing components within cells) such as MELAS syndrome (Mitochondrial Encephalopathy, myopathy, lactic acidosis and Stroke-like episodes) or Maternal inherited diabetes and deafness (MIDD).
• You have any of these symptoms after starting metformin: seizure, declined cognitive abilities, difficulty with body movements, symptoms indicating nerve damage (e.g. pain or numbness), migraine and deafness.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Metformin on its own does not cause hypoglycaemia (a blood glucose level which is too low). However, if you take Metformin together with other medicines to treat diabetes that can cause hypoglycaemia (such as sulphonylureas, insulin, meglitinides), there is a risk of hypoglycaemia. If you experience symptoms of hypoglycaemia such as weakness, dizziness, increased sweating, fast heart beating, visions disorders or difficulty in concentration, it usually helps to eat or drink something containing sugar.

If you need to have an injection of a contrast medium that contains iodine into your bloodstream, for example in the context of an X-ray or scan, you must stop taking Metformin before or at the time of the injection. Your doctor will decide when you must stop and when to restart your treatment with Metformin.

You may need more frequent blood glucose and kidney function tests, or your doctor may need to adjust the dosage of Metformin. It is especially important to mention the following:

• medicines which increase urine production (diuretics).
• medicines used to treat pain and inflammation (NSAIDs and COX-2-inhibitors, such as ibuprofen and celecoxib).
• certain medicines for the treatment of high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).
• beta-2 agonists such as salbutamol or terbutaline (used to treat asthma).
• corticosteroids (used to treat a variety of conditions, such as severe inflammation of the skin or in asthma).
• medicines that may change the amount of Metformin in your blood, especially if you have reduced kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib).
• other medicines used to treat diabetes.

Avoid excessive alcohol intake while taking Metformin since this may increase the risk of lactic acidosis (see section "Warnings and precautions").

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. During pregnancy, you need insulin to treat your diabetes instead of Metformin.

This medicine is not recommended if you are breast-feeding or if you are planning to breast-feed your baby.

Metformin on its own does not cause hypoglycaemia (a blood glucose level which is too low). This means that it will not affect your ability to drive or use machines.

However, take special care if you take Metformin together with other medicines to treat diabetes that can cause hypoglycaemia (such as sulphonylureas, insulin, meglitinides). Symptoms of hypoglycaemia include weakness, dizziness, increased sweating, fast heartbeat, vision disorders or difficulty in concentration. Do not drive or use machines if you start to feel these symptoms.

Children 10 years and over and adolescents usually start with 500 mg or 850 mg metformin once a day. The maximum daily dose is 2000 mg taken as 2 or 3 divided doses. Treatment of children between 10 and 12 years of age is only recommended on specific advice from your doctor, as experience in this age group is limited.

Adults usually start with 500 mg or 850 mg metformin two or three times a day. The maximum daily dose is 3000 mg taken as 3 divided doses.

If you have reduced kidney function, your doctor may prescribe a lower dose.

If you take insulin too, your doctor will tell you how to start Metformin.

• Your doctor will perform regular blood glucose tests and will adapt your dose of Metformin to your blood glucose levels. Make sure that you talk to your doctor regularly. This is particularly important for children and adolescents or if you are an older person.
• Your doctor will also check at least once a year how well your kidneys work. You may need more frequent checks if you are an older person or if your kidneys are not working normally.

Take Metformin with or after a meal. This will avoid you having side effects affecting your digestion.

Do not crush or chew the tablets. Swallow each tablet with a glass of water.

If you:

• Take one dose a day, take it in the morning (breakfast).
• Take two divided doses a day, take them in the morning (breakfast) and evening (dinner).
• Take three divided doses a day, take them in the morning (breakfast), at noon (lunch) and in the evening (dinner).

If, after some time, you think that the effect of Metformin is too strong or too weak, talk to your doctor or pharmacist.

500 and 850 mg: The score line is only there to help. you break the tablet if you have difficulty swallowing it whole.

If you have taken more Metformin than you should have, you may experience lactic acidosis. Symptoms of lactic acidosis are non-specific such as vomiting, bellyache (abdominal pain) with muscle cramps, a general feeling of not being well with severe tiredness, and difficulty in breathing. Further symptoms are reduced body temperature and heartbeat. If you experience some of these symptoms, you should seek immediate medical attention, as lactic acidosis may lead to coma. Stop taking Metformin immediately and contact a doctor or the nearest hospital straight away.

Do not take a double dose to make up for a forgotten dose. Take the next dose at the usual time.

• Metformin may cause a very rare (may affect up to 1 in 10,000 people), but very serious side effect called lactic acidosis (see section "Warnings and precautions"). If this happens you must stop taking Metformin and contact a doctor or the nearest hospital immediately, as lactic acidosis may lead to coma.
• digestive problems, such as feeling sick (nausea), being sick (vomiting), diarrhoea, bellyache (abdominal pain) and loss of appetite are very common (may affect more than 1 in 10 people). These side effects most often happen at the beginning of the treatment with Metformin. It helps if you spread the doses over the day and if you take Metformin with or straight after a meal.
  If symptoms continue, stop taking Metformin and talk to your doctor .
• abnormalities in liver function tests or hepatitis (inflammation of the liver; this may cause tiredness, loss of appetite, weight loss, with or without yellowing of the skin or whites of the eyes) are very rare (may affect up to 1 in 10,000 people). If this happens to you, stop taking Metformin and talk to your doctor .

Common side effects (may affect up to 1 in 10 people)

• changes in taste.
• decreased or low vitamin B12 levels in the blood (symptoms may include extreme tiredness (fatigue), a sore and red tongue (glossitis), pins and needles (paraesthesia) or pale or yellow skin). Your doctor may arrange some tests to find out the cause of your symptoms because some of these may also be caused by diabetes or due to other unrelated health problems.

Very rare side effects (may affect up to 1 in 10,000 people)

• skin reactions such as redness of the skin. (erythema), itching or an itchy rash (hives).

Limited data in children and adolescents showed that adverse events were similar in nature and severity to those reported in adults.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

The active substance is metformin hydrochloride.

• One film-coated tablet of Metformin 500 mg contains 500 mg metformin hydrochloride corresponding to 390 mg metformin base.
• One film-coated tablet of Metformin 850 mg contains 850 mg metformin hydrochloride corresponding to 662.9 mg metformin base.
• The other ingredients are povidone (K-25), magnesium stearate, hypromellose (5 mPas), Macrogol 6000, Titanium dioxide (E 171), Talc.

Metformin 500 mg film-coated tablets are white to off-white, oval film-coated tablets with break mark on one face. The tablets are supplied in blister packs of 28, 84 or 500 tablets.

Metformin 850 mg film-coated tablets are white to off-white, oblong film-coated tablets with break mark on both faces. The tablets are supplied in blister packs of 56 or 300 tablets.

Not all pack sizes may be marketed.